The long-term objective of this SBIR Phase I project is to develop antibacterial coatings for medical devices. The use of traditional antimicrobials on devices poses a substantial risk for developing drug resistant bacteria. The objective is to develop coatings that work by a different mode of action that are not likely to support the rise of resistant microorganisms. Antibacterial coatings will be produced by linking an antibacterial peptide, nisin, to surfaces via a flexible tether. Recent studies of this peptide's behavior suggest antimicrobial activity could be maintained when bound to a surface if sufficient solvent accessibility and molecular mobility are preserved. A coating of the peptide prepared in this way should be safe, functional, and long-lasting. In Phase I, chemically-modified peptide derivatives will be covalently bound to immobilized, end-group activated poly(ethylene oxide) chains. The distribution of surface tethered nisin will be quantified, and antibacterial properties of free and immobilized peptide-polymer constructs will be evaluated using a sensitive indicator strain of bacteria. The stability and duration of activity of tethered peptides will be measured in the presence of plasma. In Phase II, coating activity will be tested against clinically significant bacteria strains and in a model of central venous catheter infection in rats. This research will be conducted in close cooperation with Oregon State University thereby bringing together two important technologies that will be required for success. The collaboration will assimilate the strength of DV Biomed's industrial R&D experience in surface coating technology with OSU's unique basic science experience with the antibacterial peptide. Commercial applications for these coatings include: catheters, medical, optical and dental devices as well as research tools to investigate the mechanism of action and structural requirements for activity of antibacterial peptides. Medical device-related infections are a major problem and antibacterial coatings are needed to prevent illness, morbidity and excess cost. However, current antibacterial coatings support the rise of drug resistant bacteria, which is an important medical concern. The aim of this work is to produce alternative coatings based on natural compounds that kill bacteria. The use of such compounds in medical device coatings is expected to provide a safe, effective alternative to antibacterial drugs that will enable broader use. If successful, these coatings will improve patient care by decreasing their risk for developing hard to treat infections and will be an important milestone in the effort to control the rise of drug resistant bacteria.